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Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer.

Whittemore-Peterson Institute for Neuroimmune Diseases, University of Nevada, Reno, NV 89557, USA.
AIDS reviews (Impact Factor: 4.02). 12(3):149-52.
Source: PubMed

ABSTRACT In 2006, sequences described as xenotropic murine leukemia virus-related virus (XMRV) were discovered in prostate cancer patients. In October 2009, we published the first direct isolation of infectious XMRV from humans and the detection of infectious XMRV in patients with chronic fatigue syndrome. In that study, a combination of classic retroviral methods were used including: DNA polymerase chain reaction and reverse transcriptase polymerase chain reaction for gag and env, full length genomic sequencing, immunoblotting for viral protein expression in activated peripheral blood mononuclear cells, passage of infectious virus in both plasma and peripheral blood mononuclear cells to indicator cell lines, and detection of antibodies to XMRV in plasma. A combination of these methods has since allowed us to confirm infection by XMRV in 85% of the 101 patients that were originally studied. Since 2009, seven studies, predominantly using DNA polymerase chain reaction of blood products or tumor tissue, have reported failures to detect XMRV infection in patients with either prostate cancer or chronic fatigue syndrome. A review of the current literature on XMRV supports the importance of applying multiple independent techniques in order to determine the presence of this virus. Detection methods based upon the biological and molecular amplification of XMRV, which is usually present at low levels in unstimulated blood cells and plasma, are more sensitive than assays for the virus by DNA polymerase chain reaction of unstimulated peripheral blood mononuclear cells. When we examined patient blood samples that had originally tested negative by DNA polymerase chain reaction by more sensitive methods, we observed that they were infected with XMRV; thus, the DNA polymerase chain reaction tests provided false negative results. Therefore, we conclude that molecular analyses using DNA from unstimulated peripheral blood mononuclear cells or from whole blood are not yet sufficient as stand-alone assays for the identification of XMRV-infected individuals. Complementary methods are reviewed, that if rigorously followed, will likely show a more accurate snapshot of the actual distribution of XMRV infection in humans.

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    • "The discovery of XMRV and its potential association with PC and CFS aroused considerable excitement and promise within the research and clinical community regarding a possible infectious etiology for at least some cases of these disease or conditions. [2], [3], [33]. However, recent research findings have not supported any association between the virus and CFS or prostate cancer [7], [9], [10], [34]–[37]. "
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    ABSTRACT: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS) in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA), which regulate gene expression, were so far not identified in cells infected with XMRV in culture. Two prostate cell lines (LNCaP and DU145) and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs). miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.
    PLoS ONE 03/2012; 7(3):e32853. DOI:10.1371/journal.pone.0032853 · 3.23 Impact Factor
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    • "serology, in 67% of chronic fatigue syndrome (ME/CFS) patients compared to 3.7% in healthy controls [6]. Reports which verify [56] [102] [103] and do not verify [84, 88– 93, 105, 106, 108, 120] the original ME/CFS report have come. The situation is volatile and cannot be extensively covered here. "
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    ABSTRACT: Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect "stealth" infection, or that XMRV/HMRV never reached humans, have to be considered.
    Advances in Virology 09/2011; 2011:341294. DOI:10.1155/2011/341294
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    • "Furthermore, anti-XMRV-positive plasma samples from CFS patients blocked the binding of anti-SFFV env antibody to SFFV env on the cell surface. They claimed that FACS was one of the most sensitive blood-based assays for detection of anti-XMRV env antibody in patient plasma and could detect 82% (47/57) of XMRV infection in CFS patients [15] [16]. "
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    ABSTRACT: Xenotropic murine leukemia virus-related virus (XMRV) is a newly identified gamma retrovirus and may be associated with prostate cancer- (PC) and chronic fatigue syndrome (CFS). Since its identification in 2006 and detection of polytropic murine lenkemia virus (MLV)-like sequences in CFS patients in 2010, several test methods including nucleic acid testing methods and serological assays have been developed for detection of XMRV and/or MLV-like sequences. However, these research assays have not yet been validated and evaluated due to the lack of well-characterized reference materials. Mouse DNA contamination should be carefully checked when testing human specimens in order to avoid false-positive detection of XMRV or MLV-like sequences.
    Advances in Virology 07/2011; 2011(1687-8639):281425. DOI:10.1155/2011/281425
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